Secondary lymphoid chemokine (CCL-21/SLC) normally expressed in high endothelial venules and in T cell zones of spleen and lymph nodes, attracts Th1 T cells and mature DC. We will evaluate intratumoral administration of monocyte-derived DC gene-modified ex vivo with CCL-21 via adenoviral transduction. DC that are not fully mature have been chosen as a "vehicle" for CCL-21 in this trial based on studies indicating that this approach achieves antigen uptake and processing at the tumor site with subsequent CCL-21-mediated convergence of host T lymphocytes and mature DC. Our preliminary studies indicate that tumor antigen presentation can be achieved in situ when utilizing the tumor as an in vivo source of antigen; intratumoral administration of chemokine-transduced DC induces systemic antitumor responses and long-term specific antitumor immunity. We propose a non-randomized, dose escalation, Phase I trial evaluating intratumoral injection of CCL-21 gene-modified DC (Ad-CCL-21-DC) in advanced NSCLC patients. We will enroll 15-21 patients in three escalating dose-cohorts. Each cohort of three patients will be assigned to receive Ad-CCL-21-DC by intratumoral injection on days 0 and 7. We will start with a dose of 1 x 10[6] cells/injection for the first cohort, and increase to 1 x 10[7], followed by 3.33 x 10[7] cells/injection in subsequent cohorts. Dose escalation may proceed if all patients have been enrolled into a lower-dose cohort and no grade 3 or 4 toxicities are seen over a 28-day monitoring period in the first 3 patients assigned to that dose. Patients will be monitored for clinical and biologic responses for 56 days. Primary endpoints will be safety and maximum tolerated dose of intratumoral Ad-CCL-21-DC. Secondary endpoints include establishing the biologic and clinical activity of intratumoral Ad-CCL-21-DC. Biologic activity will be evaluated by comparing surrogate markers from pre- and post-therapy tumor samples and peripheral blood. Ag-specific IFN gamma, ELISPOT assays will be performed on peripheral blood samples on days 0 and 28. Intratumoral expression of CCL-21-dependent anti-tumor cytokines (MIG, IP-10, IL-12, IFN gamma) will be assessed in available tumor specimens on days 0 and 7. Clinical responses will be measured at day 28 and 56. This study will provide preliminary data to determine the safety of intratumoral Ad-CCL-21-DC in advanced NSCLC.